Drug Interactions Flashcards
Define the term “drug interaction” (DI)
A clinically important drug interaction is a drug effect in a real patient that is observed when two drugs are given together, which is not observed when either drug is given alone at the same dose.
The pharmacologic effect may be:
Increased or decreased
Beneficial or adverse
Deliberate or unexpected
An 18 yo young woman with depression (currently treated with phenelzine) presented to the ER with fever, agitation, disorientation, and strange myoclonic jerking movements
Without a clear dx, she was admitted for observation and IV fluids; her PCP was called, and agreed with this approach. On the floor, she was cared for by an intern (8 months) plus a junior attending resident. Admitting dx was “viral respiratory syndrome with hysterical symptoms”
On the floor, intern prescribed meperidine, an opioid, to control her shaking (good for rigors), and also to treat pleuritic pain
Both the PCP and the JAR approved this plan; intern also checked in the PDR, under “drug interactions”
At about 3 AM, patient became more agitated; nurses contacted intern twice; she had 40 other patients, did not re-evaluate patient, but did prescribe haloperidol and restraints on the phone; did not call PCP for third time
Pt fell asleep
At 6:30 AM, new VS included T 107 F, then cardiac arrest
Doctors at hospital diagnosed this as a “bad outcome” to a mysterious infection
Phenylzine == MAO-I
(NorE, Seretonin)
Presented with Seretonin Syndrome
Meperidine (opioid) x phenylzine (Seretonin, NorE)
==> Meperidine = serotonin-reuptake inhibition
==>+ Phenylzine = serotonin
In 2000, a 25-yo man was seen in the ambulatory clinic for painful white urethral discharge.
Gram stain with PMNs and diplococci
What is your diagnosis?
Treatment was begun with probenecid po, followed by procaine penicillin G suspension im.
Why give two drugs instead of one?
Gonorrhea
In 2000, a 25-yo man was seen in the ambulatory clinic for painful white urethral discharge.
Gram stain with PMNs and diplococci
What is your diagnosis?
Treatment was begun with probenecid po, followed by procaine penicillin G suspension im.
Why give two drugs instead of one?
What is recommended NOW for gonorrhea?
Gonorrhea
Tx
Probenicid == decrease renal clearance of Penicillin G (probenicid blocks transport carrier protein for Penicillin G, slowing active tubular secretion)
IM - penicillin G, procaine suspension
IV - penicillin G, salt aqueous
2018 - Ceftriaxone
Around 1969, a 61-yo African-American male was treated with hydralazine for hypertension. After a period of time, he developed SLE with nephritis (d/t reflux leading to sclerosis). The hydralazine was stopped, and Imuran™ (azathioprine – for SLE) was begun. A standard, typical dose (150 mg/day) was chosen, and the patient did well in the hospital for one week. His CBC was normal on the day of discharge [d/t ]
On the morning of discharge, the intern noted that the patient had asymptomatic hyperuricemia. Being thorough and attentive to detail, the intern wrote a new prescription for allopurinol (Zyloprim™, a drug to lower the serum level of uric acid) 300 mg once per day, and the patient was discharged.
The patient was readmitted about 1 week after discharge, with severe pancytopenia.
This was felt to represent a severe, unusual adverse reaction to the standard dose of azathioprine (Imuran™), and the drug was discontinued.
He died from bleeding secondary to severe thrombocytopenia, and sepsis from severe neutropenia.
In the CPC in the Am J Med, the final diagnosis was an unpredictable, idiosyncratic reaction to his Imuran™. The author, reviewers, and editors agreed in this final diagnosis.
Allopurinol x Azathioprine
==> allopurinol increases the toxicity of azathioprine == decreases breakdown of purines - leading to increased metabolites of azathioprine
==> increased blockage of xanthine oxidase == worsened myelosuppression
allopurinol CAN (reasonably) cause acute gouty attacks
An elderly man with severe CAD suffered a cardiac arrest, with PEA.
The resident ran the code blue; I was doing CPR as an intern and watched, trying to learn.
There was a subclavian central venous catheter in place, which I could see
The resident ordered 1 syringe of epinephrine (↑ myocardial activity), then 1 syringe of sodium bicarbonate (prevent metabolic acidosis), then 1 syringe of calcium chloride (↑ myocardial activity)
As the other inter was pushing in the 10Ml of Ca, suddenly the syringe would not empty. The clear PVC subclavian line was now filled with a white, thick fluid the intern couldn’t’ push it because the syringe would not clear so the resident just pushed harder and it cleared
Epinephrine likes acidic environment
Sodium bicarbonate (pH = 13)
==> inactivated
CaCl2 + NaHCO3 ==> CaCO3 + NaCl + HCl
Pharmaceutical effect
Calcium carbonate
== need to FLUSH between drugs
